Tumor Microenvironment-Activated Nanoparticles Loaded with an Iron-Carbonyl Complex for Chemodynamic Immunotherapy of Lung Metastasis of Melanoma In Vivo

体内 癌症研究 免疫疗法 黑色素瘤 材料科学 氧化应激 谷胱甘肽 活性氧 化学 铁质 转移 医学 癌症 免疫系统 免疫学 生物 内科学 生物化学 冶金 生物技术
作者
Tianli Zhai,Wei Zhong,Yucong Gao,Han Zhou,Zhiguo Zhou,Xiaoming Liu,Shiping Yang,Hong Yang
出处
期刊:ACS Applied Materials & Interfaces [American Chemical Society]
卷期号:13 (33): 39100-39111 被引量:17
标识
DOI:10.1021/acsami.1c11485
摘要

In this work, a nanoplatform (FeCORM NPs) loaded with an iron-carbonyl complex was constructed. By exploiting chemodynamic therapy (CDT) and immunogenic cell death (ICD)-induced immunotherapy (IMT), the nanoparticles exhibited excellent efficacy against lung metastasis of melanoma in vivo. The iron-carbonyl compound of the nanomaterials could be initiated by both glutathione (GSH) and hydrogen peroxide (H2O2) to release CO and generate ferrous iron through ligand exchange and oxidative destruction pathways. The released CO caused mitochondria damage, whereas the generated ferrous iron led to oxidative stress via the Fenton reaction. On the other hand, the nanomaterials induced ICD-based IMT, which worked jointly with CDT to exhibit excellent effects against lung metastasis of melanoma through a mouse model. This work demonstrated how a nanoplatform, simple and stable but showing excellent efficacy against tumors, could be built using simple building blocks via a self-assembling approach. Importantly, the system took advantage of relatively high levels of GSH and H2O2 in tumors to initiate the therapeutic effects, which rendered the nanoplatform with a capability to differentiate normal cells from tumor cells. In principle, the system has great potential for future clinical applications, not only in the treatment of lung metastasis of melanoma but also in suppressing other types of tumors.
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